Nucleotide sequence of the genome of simian T-lymphotropic virus type III from African green monkeys (STLV-IIIagm) and of an HIV-2 isolate (HIV-2 SBL6669) have been carried out in order to compare them with HIV-1 and help understand the natural history and pathobiology of these viruses, as well as their role in the AIDS epidemic. Work has been initiated to try to construct biologically active clones of STLV-III and HIV-2. A second project has been to study the ability of HIV-1 clonal populations to generate mutants resistant to the host immune response. One such mutant has been obtained and thoroughly characterized and the specific mutation responsible for neutralization resistance is being identified. A third project is to identify the genetic determinants of macrophage-tropic HIV-1 which confer the ability to grow in macrophages. Several DNA clones of such viruses have been obtained, and are currently being tested for their biological activity.